Intravenous sodium valproate versus intravenous phenytoin in the treatment of children's status epilepticus: a multicenter randomized controlled clinical trial

Abstract

Background: Status epilepticus is a life-threatening condition and one of the most frequent neurological emergencies among pediatric population, with an increase of morbidity and mortality. It has an incidence rate of 17-23 episodes/100.000 children per year in developed countries. The status epilepticus requires a promptly management with stabilization of vital functions and administration of antiepileptic drugs. The first-line antiepileptic drugs are the benzodiazepines, but if after two doses of benzodiazepines the status epilepticus persists, the second-line antiepileptic drugs must be administrated. Among these drugs, two of the most frequently used are intravenous sodium valproate and intravenous phenytoin. However, there is no consensus to decide which of them should be preferably used and there is a lack of standardized and universally accepted protocols. For example, valproate is preferred in Catalonia while phenytoin is preferred in United States of America (USA). Objective: The principal objective of this study is to compare the efficacy (termination of status epilepticus) of intravenous sodium valproate and intravenous phenytoin in the treatment of benzodiazepine refractory convulsive status epilepticus in pediatric population. Design: Multicenter, controlled, triple-blind, randomized clinical trial with the Hospital Universitari de Girona Doctor Josep Trueta (Girona) as the reference center. The other participating hospitals are: Hospital Universitari Vall d’Hebron (Barcelona), Hospital Sant Joan de Déu (Barcelona), Hospital Universitari Arnau de Vilanova (Lleida), Hospital Universitari Parc Taulí (Sabadell) and Hospital Universitari Joan XXIII de Tarragona (Tarragona). Methods: Patients enrolled in this study will be randomized in two groups (A and B). In order to terminate the status epilepticus, the group A will receive an infusion of intravenous sodium valproate while the group B will receive an infusion of intravenous phenytoin. The efficacy and safety of these drugs of study will be evaluated and recorded and the patients will be followed-up during one month to evaluate their mortality and neurological outcome. Participants: Children (≥ 1 years old and < 15 years old) suffering a convulsive status epilepticus refractory to two doses of a benzodiazepine (midazolam or diazepam) attended by the hospitals that will take part of this study